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Many clinical studies have been done on the efficacy of adaptogens, and the clinical levels at which these effects are shown in humans. Below is a list of double-blind case studies and reviews done on adaptogens both in general, as well as on several of the specific adaptogenic plants found in Elements tonics. The clinically-effective levels of the adaptogens in our formulas are based around this scientific research.


The beneficial stress-protective effect of adaptogens is related to regulation of homeostasis via several mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the control of key mediators of stress response such as molecular chaperons (e.g. Hsp70), stressactivated c-Jun N-terminal protein kinase (JNK1), Forkhead Box O transcription factor DAF-16, cortisol and nitric oxide (NO). The key point of action of phytoadaptogens appears to be their upregulating and stress-mimetic effects on the "stress-sensor" protein Hsp70, which plays an important role in cell survival and apoptosis. Hsp70 inhibits the expression of NO synthase II gene and interacts with glucocorticoid receptors directly and via the JNK pathway, thus affecting the levels of circulating cortisol and NO. Prevention of stress-induced increase in NO, and the associated decrease in ATP production, results in increased performance and endurance. Adaptogen-induced up-regulation of Hsp70 triggers stress-induced JNK-1 and DAF-16-mediated pathways regulating the resistance to stress and resulting in enhanced mental and physical performance and, possibly, increased longevity.

Source: Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009 Sep;4(3):198-219. Epub 2009 Sep 1. Review.


It is concluded that repeated administration of R. ROSEA extract SHR-5 exerts an anti-fatigue effect that increases mental performance, particularly the ability to concentrate, and decreases cortisol response to awakening stress in burnout patients with fatigue syndrome.

Source: A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Olsson EM, von Schéele B, Panossian AG. Planta Med. 2009 Feb;75(2):105-12. doi: 10.1055/s-0028-1088346. Epub 2008 Nov 18. 

Link to Clinical Case Study About Rhodiola

The objective was to investigate the stimulating and normalizing effect of the adaptogen Rhodiola rosea extract SHR-5 in foreign students during a stressful examination period. The study was performed as a double-blind, randomized and placebo-controlled with low repeated dose regime. The study drug and the placebo were taken for 20 days by the students during an examination period. The physical and mental performance were assessed before and after the period, based on objective as well as on subjective evaluation. The most significant improvement in the SHR-5 group was seen in physical fitness, mental fatigue and neuro-motoric tests (p <0.01). The self-assessment of the general well-being was also significantly (p < 0.05) better in the verum group.

Source: Spasov AA, Wikman GK, Mandrikov VB, et al. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine 2000;7:85-89 

Link to Clinical Case Study About Rhodiola

The perceptive and cognitive cerebral functions mentioned above (part of the Fatigue Index) were investigated using 5 different tests. A statistically significant improvement in these tests was observed in the treatment group (RRE) during the first two weeks period. No side-effects were reported for either treatment noted. These results suggest that RRE can reduce general fatigue under certain stressful conditions.

Source: Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H. Phytomedicine. 2000 Oct;7(5):365-71.

Link to Clinical Case Study About Rhodiola 


The treatment group that was given the high-concentration full-spectrum Ashwagandha root extract exhibited a significant reduction (P<0.0001) in scores on all the stress-assessment scales on Day 60, relative to the placebo group. The serum cortisol levels were substantially reduced (P=0.0006) in the Ashwagandha group, relative to the placebo group. The adverse effects were mild in nature and were comparable in both the groups. No serious adverse events were reported.

Source: Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebocontrolled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 2012;34(3):255-62

Link to Clinical Case Study About Ashwagandha

Methods: Researchers evaluated a series of objective and subjective variables

Results: Significant reduction in cortisol and C-reactive protein, and significant increase in DHEA at all doses Significant reduction in fasting blood sugar, cholesterol, and triglycerides at the 125 mg twice daily dose and 250 mg twice daily dose. Significant reduction in stress, anxiety, irritability, inability to concentrate, forgetfulness, sleeplessness, fatigue, and other subjective indicators of stress at all doses

Source: Auddy B, et al. 2008. A standardized Withania somnifera extract significantly reduces stressrelated parameters in chronically stressed humans; A double-blind, randomized, placebocontrolled study. JANA 11:50-56)

A total of 52 subjects under chronic stress received either Ashwagandha (300 mg) or placebo twice daily. Primary efficacy measures were Perceived Stress Scale and Food Cravings Questionnaire. Secondary efficacy measures were Oxford Happiness Questionnaire, Three-Factor Eating Questionnaire, serum cortisol, body weight, and body mass index. Each subject was assessed at the start and at 4 and 8 weeks. The treatment with Ashwagandha resulted in significant improvements in ADAPTOGENS + STRESS / CORTISOL CASE STUDIES + REVIEWS primary and secondary measures. Also, the extract was found to be safe and tolerable. The outcome of this study suggests that Ashwagandha root extract can be used for body weight management in adults under chronic stress.

SourceBody Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial. Choudhary D, Bhattacharyya S, Joshi K. J Evid Based Complementary Altern Med. 2017 Jan;22(1):96-106. Epub 2016 Apr 6. 

Link to Clinical Case Study About Ashwagandha


Intergroup comparison revealed a significant improvement of the following cognitive parameters in the EtOS (ethanolic extract of holy basil) as compared to the placebo: reaction time (RT) and error rate (ER) of Sternberg test, RT of neutral task of Stroop, RT and ER of interference task of Stroop. The intra-group comparison of P300 latency, salivary cortisol, and State-Trait Anxiety Inventory showed improvement over time in the EtOS group alone, though the inter-group difference was significant in the P300 latency alone. There were no changes in heart rate (HR), AHR, or galvanic skin response (GSR) or AGSR.

Source: Holy basil (Ocimum sanctum Linn.) leaf extract enhances specific cognitive parameters in healthy adult volunteers: A placebo controlled study. Sampath S, Mahapatra SC, Padhi MM, Sharma R, Talwar A. Indian J Physiol Pharmacol. 2015 Jan-Mar;59(1):69-77.

Link to Clinical Case Study About Holy Basil 


Good scientific evidence has been documented in trails in which Schisandra chinensis and Eleutherococcus senticosus increased endurance and mental performance in patients with mild fatigue and weakness.

Source: Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Panossian A, Wikman G. Curr Clin Pharmacol. 2009 Sep;4(3):198- 219. Epub 2009 Sep 1. Review. 

Link to Clinical Case Study About Schisandra